Abstract
Interleukin 2 signaling is believed to be critically involved in several aspects of CD25+ CD4+ regulatory T cell biology, such as intrathymic development, peripheral survival and suppressive function. Here we have analyzed the effects of interleukin 2 or CD25 deficiency on agonist-driven thymic development and the peripheral homeostasis of an antigen-specific population of regulatory T cells positive for forkhead family transcription factor Foxp3 and have correlated our observations with polyclonal suppressor populations. We found that the differentiation, acquisition of functional capacity and formation of a sizeable pool of suppressor T cells in the thymus was independent of interleukin 2 signaling, but that interleukin 2 was essential for the survival of mature Foxp3+ regulatory T cells.
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Acknowledgements
We thank H. von Boehmer (Dana Farber Cancer Institute, Boston, Massachusetts) for TCR-HA × pgk-HA mice and for discussions. Supported by Boehringer Ingelheim (Research Institute of Molecular Pathology), the Austrian National Science Fund (Sonderforschungsbereich F023 and Z58-B01) and the European Union (FP6 Integrated Project Eurothymaide).
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Supplementary information
Supplementary Fig. 1
CD25+Foxp3+ Treg are greatly reduced in the periphery of IL-2 deficient mice. (PDF 483 kb)
Supplementary Fig. 2
Phenotype of lymph node cells in Il2ra−/− TCR-HA × pgk-HA mice. (PDF 742 kb)
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D'Cruz, L., Klein, L. Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol 6, 1152–1159 (2005). https://doi.org/10.1038/ni1264
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DOI: https://doi.org/10.1038/ni1264
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